On July 30, Anavex Life Sciences reported positive preclinical results relating to human translatable biomarkers for individuals with FXS for ANAVEX 2-73 (blarcamesine) in a disease model of Fragile X syndrome (FXS). Fragile X syndrome is the most common form of inherited intellectual disability and the most frequent single gene cause of autism spectrum disorder with an estimated population of approximately 62,500 in the US and 1,088,500 worldwide. Characterized by a range of cognitive, behavioral, and sensory challenges, including learning difficulties, anxiety, hyperactivity and sensitivity to sensory stimuli, there is currently no approved treatment for Fragile X syndrome.
The findings, presented at the 19th NFXF International Fragile X Conference, referenced positive results in directly to humans’ translatable electroencephalogram (EEG) biomarkers present in both individuals with FXS and animal models of FXS.
Anavex Life Sciences is a publicly-traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia and other central nervous system (CNS) diseases. Its lead drug candidate, ANAVEX 2-73, an orally-available drug, has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer’s disease, a Phase 2 proof-of-concept study in Parkinson’s disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 study in pediatric patients with Rett syndrome.
Fragile X Syndrome and Autism Spectrum Disorder Explained
Fragile X Syndrome is the most prevalent inherited intellectual disability and the leading single-gene cause of autism, which affects about 1 in 4,000 males and 1 in 6,000 females.
While autism spectrum disorder is identified behaviorally, Fragile X syndrome is a medical/genetic diagnosis. Numerous studies over the past decades have explored the connection between the two. Autism is significantly more common in boys with Fragile X syndrome compared to girls. The CDC reports that a national parent survey indicated 46% of males and 16% of females with Fragile X Syndrome have been diagnosed or treated for autism spectrum disorder.2
Relevance of Study Model
The research examined the impact of ANAVEX 2-73 on brain activity in a mouse model of Fragile X Syndrome (FXS) using electroencephalography (EEG), a non-invasive method for measuring electrical brain signals. EEG recordings from mice treated with ANAVEX 2-73 revealed significant, dose-dependent enhancements in several critical brain function biomarkers compared to untreated mice.
Notably, improvements were observed in the auditory steady state response (ASSR) EEG test, which is crucial for treating central nervous system (CNS) disorders. In FXS and other CNS disorders, the brain struggles to synchronize sensory inputs like sounds, leading to sensory overload and hypersensitivity. In this study, ANAVEX 2-73 significantly enhanced neural synchrony in response to sounds in the frontal and auditory cortices of the brain in a dose-dependent manner.
The dysfunction of cells that manage the balance of excitatory-inhibitory signaling is linked to these hypersensitivities characteristic of various neurodevelopmental disorders, including FXS. This new data indicates that ANAVEX 2-73 restores this balance and improves neuronal connectivity, which is directly applicable to humans and showcases the therapeutic potential of ANAVEX 2-73 in addressing behavioral, sensory, and cognitive abnormalities in individuals with FXS.
“These additional non-invasive biomarker findings in Fragile X syndrome provide further evidence of potential to expand the therapeutic profile of ANAVEX 2-73 into the largest portion of addressable market of autism spectrum disorder, Fragile X syndrome,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “We look forward to initiating a double-blind, placebo-controlled ANAVEX 2-73 study in Fragile X syndrome. This is further evidence of the potential of ANAVEX 2-73 as a platform technology of precision medicine.”
Previous studies, published in journals such as Nature Scientific Reports and the American Journal of Medical Genetics, have demonstrated the preclinical efficacy of ANAVEX 2-73 in an animal model of FXS. These studies showed that ANAVEX 2-73 could mitigate behavioral deficits and fluid biomarker features of FXS. The dose-dependent effects of ANAVEX 2-73 led to a reversal of hyperactivity, restoration of associative learning, and reduction of anxiety in a mouse model of FXS, along with improvements in key blood signaling biomarkers measurable in FXS patients. Based on the results, Anavex plans to initiate a clinical trial to evaluate the safety and efficacy of ANAVEX 2-73 in individuals with FXS.